Iontophoretic delivery device and method of hydrating same

ABSTRACT

A dry-state iontophoretic drug delivery device (10, 70, 80) is provided. The device has drug and electrolyte reservoirs (15, 16) which are initially in a non-hydrated condition. A liquid-containing pouch (21, 22) is provided. In certain embodiments the liquid is contained in breakable capsules within the pouch. Water or other liquid can be released from the capsules in the pouch by squeezing or flexing the pouches (21,22). Alternatively, the liquid can be released from the pouches (21,22) using pouch piercing pins (36,37). The liquid released from the pouches (21,22) hydrates the drug and electrolyte reservoirs (15, 16) and activates the device. In another embodiment, the device (20, 20a) has liquid-containing gel layers (31,32) which are initially separated from their respective electrode assemblies (8, 9). Liquid-wicking pathways (27,28) are provided to carry the liquid from the gel layers (31,32) to the drug and electrolyte layers (15, 16).

This is a division of U.S. patent application Ser. No. 07/605,046 filedOct. 29, 1990 U.S. Pat. No. 5,128,537.

TECHNICAL FIELD

This invention relates to a device for delivering an agent transdermallyor transmucosally by iontophoresis. More particularly, this inventionrelates to an electrically powered iontophoretic delivery device havinga liquid reservoir which is initially isolated from other initially drycomponents of the device. The liquid in the liquid reservoir is used tohydrate the dry components, allowing the device to be activated justbefore use.

BACKGROUND ART

Iontophoresis, according to Dorland's Illustrated Medical Dictionary, isdefined to be "the introduction, by means of electric current, of ionsof soluble salts into the tissues of the body for therapeutic purposes."Iontophoretic devices have been known since the early 1900's. Britishpatent specification No. 410,009 (1934) describes an iontophoreticdevice which overcame one of the disadvantages of such early devicesknown to the art at that time, namely the requirement of a special lowtension (low voltage) source of current which meant that the patientneeded to be immobilized near such source. The device of that Britishspecification was made by forming a galvanic cell from the electrodesand the material containing the medicament or drug to be deliveredtransdermally. The galvanic cell produced the current necessary foriontophoretically delivering the medicament. This ambulatory device thuspermitted iontophoretic drug delivery with substantially lessinterference with the patient's daily activities.

More recently, a number of United States patents have issued in theiontophoresis field, indicating a renewed interest in this mode of drugdelivery. For example, U.S. Pat. No. 3,991,755 issued to Vernon et al;U.S. Pat. No. 4,141,359 issued to Jacobsen et al; U.S. Pat. No.4,398,545 issued to Wilson; and U.S. Pat. No. 4,250,878 issued toJacobsen disclose examples of iontophoretic devices and someapplications thereof. The iontophoresis process has been found to beuseful in the transdermal administration of medicaments or drugsincluding lidocaine hydrochloride, hydrocortisone, fluoride, penicillin,dexamethasone sodium phosphate, insulin and many other drugs. Perhapsthe most common use of iontophoresis is in diagnosing cystic fibrosis bydelivering pilocarpine salts iontophoretically. The pilocarpinestimulates sweat production; the sweat is collected and analyzed for itschloride content to detect the presence of the disease.

In presently known iontophoretic devices, at least two electrodes areused. Both of these electrodes are disposed so as to be in intimateelectrical contact with some portion of the skin of the body. Oneelectrode, called the active or donor electrode, is the electrode fromwhich the ionic substance, medicament, drug precursor or drug isdelivered into the body by iontophoresis. The other electrode, calledthe counter or return electrode, serves to close the electrical circuitthrough the body. In conjunction with the patient's skin contacted bythe electrodes, the circuit is completed by connection of the electrodesto a source of electrical energy, e.g., a battery. For example, if theionic substance to be delivered into the body is positively charged(i.e., a cation), then the anode will be the active electrode and thecathode will serve to complete the circuit. If the ionic substance to bedelivered is negatively charged (i.e., an anion), then the cathode willbe the active electrode and the anode will be the counter electrode.

Alternatively, both the anode and cathode may be used to deliver drugsof opposite charge into the body. In such a case, both electrodes areconsidered to be active or donor electrodes. For example, the anode candeliver a positively charged ionic substance into the body while thecathode can deliver a negatively charged ionic substance into the body.

It is also known that iontophoretic delivery devices can be used todeliver an uncharged drug or agent into the body. This is accomplishedby a process called electroosmosis. Transdermal delivery of neutralcompounds by the phenomenon of electroosmosis is described by HermannRein in Zeitschrift fur Biologie, Bd. 81, pp 125-140 (1924) and thetransdermal delivery of nonionic polypeptides by the phenomenon ofelectroosmosis is described in Sibalis et al. U.S. Pat. Nos. 4,878,892and 4,940,456. Electroosmosis is the transdermal flux of a liquidsolvent (e.g., the liquid solvent containing the uncharged drug oragent) which is induced by the presence of an electric field imposedacross the skin by the donor electrode. As used herein, the terms"iontophoresis" and "iontophoretic" encompass both the delivery ofcharged ions as well as the delivery of uncharged molecules by theassociated phenomenon of electroosmosis.

Iontophoretic delivery devices generally require a reservoir or sourceof the beneficial agent (which is preferably an ionized or ionizableagent or a precursor of such agent) to be iontophoretically delivered orintroduced into the body. Examples of such reservoirs or sources ofionized or ionizable agents include a pouch or cavity as described inthe previously mentioned Jacobsen U.S. Pat. No. 4,250,878, a poroussponge or pad as disclosed in Jacobsen et al. U.S. Pat. No. 4,141,359,or a pre-formed gel body as described in Webster U.S. Pat. No. 4,383,529and Ariura et al. U.S. Pat. No. 4,474,570. Such drug reservoirs areelectrically connected to the anode or the cathode of an iontophoresisdevice to provide a fixed or renewable source of one or more desiredagents.

Iontophoretic delivery devices which are attachable at a skin surfaceand rely on electrolyte fluids to establish electrical contact with suchskin surfaces can be divided into at least two categories. The firstcategory includes those devices which are prepackaged with the liquidelectrolyte contained in the electrode receptacle. The second type ofdevice uses dry-state electrodes whose receptacles are customarilyfilled with liquid drug/electrolyte immediately prior to application tothe body. With both types of devices, the user currently experiencesnumerous problems which make their use both inconvenient andproblematic.

With respect to the prefilled device, storage is a major concern. Manydrugs have poor stability when in solution. Accordingly, the shelf lifeof prefilled iontophoretic drug delivery devices is unacceptably short.Corrosion of the electrodes and other electrical components is also apotential problem with prefilled devices. For example, the returnelectrode assembly will usually contain an electrolyte salt such assodium chloride which over time can cause corrosion of metallic andother electrically conductive materials in the electrode assembly.Leakage is another serious problem with prefilled iontophoretic drugdelivery devices. Leakage of drug or electrolyte from the electrodereceptacle can result in an inoperative or defective state. Furthermore,such prefilled devices are difficult to apply because the protectiveseal which covers the electrode opening and retains the fluid within thereceptacle cavity must be removed prior to application on the skin.After removal of this protective seal, spillage often occurs inattempting to place the electrode on the skin. Such spillage impairs thedesired adhesive contact of the electrode to the skin and also voids aportion of the receptacle cavity. The consequent loss of drug orelectrolyte fluid tends to disrupt electrical contact with the electrodeplate contained therein and otherwise disrupts the preferred uniformpotential gradient to be applied.

Although dry-state electrodes have numerous advantages in ease ofstorage, several problems remain. For example, the drug and electrolytereceptacles of such a device are conventionally filled through anopening prior to application of the device to the patient's skin.Therefore, the same problem of spillage and loss of drug or electrolyteupon application occurs as with the prefilled electrode.

Frequently, such electrodes are not well structured to develop theproper uniform current flow required in iontophoresis applications. Suchnonuniform current flow may result from the occurrence of air pocketswithin the receptacle cavity at the skin surface. Such effects areparticularly troublesome in iontophoresis applications, where anonuniform current distribution may result in excessive skin irritationor "burning".

More recently, iontophoretic delivery devices have been developed inwhich the donor and counter electrode assemblies have a "multilaminate"construction. In these devices, the donor and counter electrodeassemblies are each formed of multiple layers of (usually) polymericmatrices. For example, Parsi U.S. Pat. No. 4,731,049 discloses a donorelectrode assembly having hydrophilic polymer based electrolytereservoir and drug reservoir layers, a skin-contacting hydrogel layer,and optionally one or more semipermeable membrane layers. In addition,Ariura et al, U.S. Pat. No. 4,474,570 discloses a device wherein theelectrode assemblies include a conductive resin film electrode layer, ahydrophilic gel reservoir layer, an aluminum foil conductor layer and aninsulating backing layer.

The drug and electrolyte reservoir layers of iontophoretic deliverydevices have typically been formed of hydrophilic polymers. See forexample, Ariura et al, U.S. Pat. No. 4,474,570; Webster U.S. Pat. No.4,383,529 and Sasaki U.S. Pat. No. 4,764,164. There are several reasonsfor using hydrophilic polymers. First, water is a biocompatible, highlypolar solvent and therefore preferred for ionizing many drug salts.Secondly, hydrophilic polymer components (i.e., the drug reservoir inthe donor electrode and the electrolyte reservoir in the counterelectrode) can be hydrated while attached to the body by absorbing waterfrom the skin or from a mucosal membrane. For example, skin contactingelectrodes can be hydrated by absorbing sweat or water fromtransepidermal water loss. Similarly, electrodes attached to an oralmucosal membrane can be hydrated by absorbing saliva. Once the drug andelectrolyte reservoirs become hydrated, ions are able to move throughthe reservoirs and across the tissue, enabling the device to deliveragent to the body. Hydrogels have been particularly favored for use asthe drug reservoir matrix and electrolyte reservoir matrix iniontophoretic delivery devices, in part due to their high equilibriumwater content and their ability to absorb water from the body. Inaddition, hydrogels tend to have good biocompatibility with the skin andwith mucosal membranes. However, since many drugs and certain electrodecomponents are unstable in the presence of water, iontophoretic drugdelivery devices having a drug reservoir formed of a prehydratedhydrogel may also have an unacceptably short shelf life. One solution tothe drug stability problem is to use hydrophilic polymer drug andelectrolyte reservoirs which are in a substantially dry state, i.e. in anon-hydrated condition. The drug and/or electrolyte can be dry blendedwith the hydrophilic polymer and then cast or extruded to form anon-hydrated, though hydratable, drug or electrolyte containingreservoir. Unfortunately, the non-hydrated hydrophilic polymercomponents must first absorb sufficient quantities of water from thebody before the device can operate to deliver drug. This deliverystart-up period can take in excess of 8 hours. This delay makes manydevices unsuited for their intended purpose. For example, when using aniontophoretic delivery device to apply a local anesthetic in preparationfor a minor surgery (e.g., surgical removal of a mole), the surgeon andthe patient must wait until the drug and electrolyte reservoirs of thedelivery device become sufficiently hydrated before the anesthetic isdelivered in sufficient quantities to induce anesthesia. Similar delaysare encountered with other drugs.

In response to these difficulties, Konno et al. in U.S. Pat. No.4,842,577 disclose in FIG. 4 an iontophoretic electrode assembly havinga substantially non-hydrated drug containing matrix and a separate waterreservoir which is initially sealed, using a foil sheet, from the drugcontaining portions of the electrode. Unfortunately, this electrodedesign is not only difficult to manufacture but also is subject tosevere handling restrictions. In particular, there is a tendency for thefoil seal to be inadvertently broken during manufacture, packaging andhandling of the electrode. This can have particularly drasticconsequences especially when the seal is broken during manufacture ofthe device. Once the seal is broken, water is wicked into thedrug-containing reservoir which can cause degradation of the drug and/orother components before the device is ever used.

Another disadvantage of using non-hydrated hydrophilic polymercomponents is that they have a tendency to delaminate from other partsof the electrode assembly during hydration. For example, when utilizinga drug reservoir matrix or an electrolyte reservoir matrix composed of ahydrophilic polymer, the matrix begins to swell as it absorbs water fromthe skin. In the case of hydrogels, the swelling is quite pronounced.Typically, the drug or electrolyte reservoir is in either directcontact, or contact through a thin layer of an ionically conductiveadhesive, with an electrode. Typically, the electrode is composed ofmetal (e.g., a metal foil or a thin layer of metal deposited on abacking layer) or a hydrophobic polymer containing a conductive filler(e.g., a hydrophobic polymer loaded with carbon fibers and/or metalparticles). Unlike the hydrophilic drug and electrolyte reservoirs, theelectrodes do not absorb water and do not swell. The different swellingproperties of the hydrophilic reservoirs and the electrodes results inshearing along their contact surfaces. In severe cases, the shearing canresult in the complete loss of electrical contact between the electrodeand the drug/electrolyte reservoir resulting in an inoperable device.

DISCLOSURE OF THE INVENTION

Thus, it is an object of the present invention to provide aniontophoretic drug delivery device with agent-containing electrodecomponents which are manufactured in an initially non-hydrated or drystate but which can be quickly hydrated prior to placement on the body.

It is another object of this invention to provide an improved method ofquickly hydrating the electrodes in an iontophoretic delivery device inorder to minimize the "start-up" delay of an iontophoretic deliverydevice.

It is a further object of this invention to provide an iontophoreticdrug delivery device which cannot be inadvertently hydrated prior toactual use.

It is a still further object of this invention to provide a method ofhydrating the hydrophilic components of a dry state multilaminateiontophoresis electrode assembly without the delamination problemsencountered with the prior art electrodes.

These and other objects are met by an electrically powered iontophoreticagent delivery device and a method of hydrating same. In accordance withone embodiment of the invention, the delivery device includes at leastone multilaminate dry state electrode assembly and a source ofelectrical power which is electrically connected to the electrodeassembly. The electrode assembly includes a reservoir layer comprised ofa substantially non-hydrated hydratable matrix adapted to contain anagent to be delivered. The electrode assembly is adapted to be placed inagent transmitting relation with a body surface, such as intact skin ora mucosal membrane, for delivery of agent therethrough. The electrodeassembly also includes an electrode layer in electrical contact withboth the power source and the reservoir layer.

The electrode assembly has a means for hydrating the substantiallynon-hydrated matrix. Said means for hydrating the matrix includes apreformed passageway through the electrode layer. The passagewayestablishes fluid communication between the exterior of the device andthe non-hydrated matrix. The electrode assembly is activated byintroducing a liquid from an external source through the preformedpassageway through the electrode layer into the hydratable reservoirlayer.

Preferably, the liquid comprises water. In the case of a donor electrodeassembly, the agent preferably comprises a drug. In the counterelectrode assembly, the agent preferably comprises an electrolyte salt.Most preferably, both the agent and the electrolyte salt are soluble inthe liquid. The agent and/or the electrolyte salt may be present in thenon-hydrated matrix either before hydration or maybe added to thenon-hydrated matrix with the liquid at the time of hydration. When thenon-hydrated matrix already contains the agent, the liquid preferablycomprises deionized water. When the non-hydrated matrix initiallycontains no agent, the liquid preferably comprises an aqueous solutionor suspension of a drug or an electrolyte salt. Most preferably, thematrix of the reservoir layer is comprised of a hydrophilic polymer.

In accordance with a second embodiment of the invention, a multilaminatedry state electrode assembly for an electrically powered iontophoreticagent delivery device, and a method of hydrating the electrode assembly,are provided. The electrode assembly is adapted to be placed in agenttransmitting relation with a body surface such as intact skin or amucosal membrane, for delivery of agent therethrough. The electrodeassembly includes an electrode layer in electrical contact with anelectrical power source and adapted to be placed in electrical contactwith a reservoir layer. The reservoir layer is adapted to contain anagent to be delivered. The reservoir layer comprises a substantiallynon-hydrated, hydratable matrix which is initially separated from theelectrode layer and the power source. The reservoir layer has anexposable surface for introducing a liquid thereto in order to hydratethe reservoir layer. After hydration, the reservoir layer is placed inelectrical contact with the electrode layer.

Also provided is a method for hydrating the device. The method includesseparating the reservoir layer from the electrode layer while thereservoir layer is in a substantially non-hydrated condition. Ahydrating liquid is introduced into the reservoir layer in an amountsufficient to permit ion transport through the reservoir layer.Thereafter, the hydrated reservoir layer is secured in electricalcontact with the electrode layer.

Preferably, the hydrating liquid comprises water. In the case of a donorelectrode assembly, the agent preferably comprises a drug. In thecounter electrode assembly, the agent preferably comprises anelectrolyte salt. Most preferably, both the agent and the electrolytesalt are soluble in the liquid. The agent and/or the electrolyte saltmay be present in the non-hydrated matrix either before hydration or maybe added to the non-hydrated matrix with the liquid at the time ofhydration. When the non-hydrated matrix already contains the agent, theliquid preferably comprises deionized water. When the non-hydratedmatrix initially contains no agent, the liquid preferably comprises anaqueous solution or suspension of a drug or an electrolyte salt. Mostpreferably, the matrix of the reservoir layer is a hydrophilic polymer.This embodiment of the invention has particular utility where thehydrophilic polymer has a tendency to swell upon hydration. Mostpreferably, the hydrated reservoir layer is secured in electricalcontact with the electrode layer after the swelling of the reservoirlayer is substantially complete.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic top view of an iontophoretic drug delivery deviceaccording to the present invention;

FIG. 2 is a schematic end view of the device shown in FIG. 1;

FIG. 3 is a schematic end view of another iontophoretic delivery deviceaccording to the present invention;

FIG. 4 is a schematic top view of a portion of another iontophoreticdelivery device according to the present invention.

FIG. 5 is a schematic side view of the device shown in FIG. 4, duringassembly;

FIG. 6 is a schematic side view of another iontophoretic delivery deviceaccording to the present invention;

FIG. 7 is a schematic side view of another iontophoretic delivery deviceaccording to the present invention;

FIG. 8 is a schematic side view of another iontophoretic delivery deviceaccording to the present invention; and

FIG. 9 is a schematic side view of another iontophoretic delivery deviceaccording to the present invention.

In the figures, like elements are designated by the same referencenumber in the several drawings.

MODES FOR CARRYING OUT THE INVENTION

FIG. 6 is a schematic view of an iontophoretic delivery device 10 fordelivering a beneficial agent through a body surface such as intact skinor a mucosal membrane. Iontophoretic delivery device 10 includes a donorelectrode assembly 8 and a counter electrode assembly 9. The donorelectrode assembly 8 and the counter electrode assembly 9 are physicallyattached to insulator 26 and form a single self-contained unit.Insulator 26 prevents the electrode assemblies 8 and 9 from shortcircuiting the device by preventing direct electrical and/or iontransport between the electrode assemblies 8 and 9. Electrode assemblies8 and 9 are connected in series, by appropriate electrical conductors,with an electrical power source. The power source and the electricalconductors are schematically shown as layer 14. The power source used topower device 10 is typically one or more low voltage batteries. A waterimpermeable backing layer 13 preferably covers layer 14 with itsassociated electrical components.

The donor electrode assembly 8 includes an electrode layer 11 and areservoir layer 15. The reservoir 15 contains the beneficial agent to beiontophoretically delivered by device 10. A rate controlling membranelayer 19 is optionally positioned between the reservoir layer 15 and thebody surface for controlling the rate at which the agent is delivered tothe body surface or for preventing the delivery of agent to the bodysurface when the device is turned off. Counter electrode assembly 9contacts the body surface at a location spaced apart from electrodeassembly 8. Counter electrode assembly 9 includes an electrode layer 12and a reservoir layer 16. Device 10 can be adhered to the body surfaceby means of ion-conducting adhesive layers 17 and 18. As an alternativeto the ion-conducting adhesive layers 17 and 18 shown in FIG. 6, device10 may be adhered to the body surface using an adhesive overlay. Any ofthe conventional adhesive overlays used to secure passive transdermaldelivery devices to the skin may be used.

When the device 10 is in storage, no current flows because the devicedoes not form a closed circuit. When the device 10 is placed on the skinor mucosal membrane of a patient and the electrode assemblies 8 and 9are sufficiently hydrated to allow ions to flow through the variouslayers of electrode assemblies 8 and 9, the circuit between theelectrodes is closed and the power source begins to deliver currentthrough the device and through the body of the patient. The donor andcounter electrode assemblies 8 and 9 normally include a strippablerelease liner, not shown, which is removed prior to application ofelectrode assemblies 8 and 9 to a body surface.

As shown in FIG. 6, the donor electrode assembly 8 includes a flexiblepouch 21 containing a plurality of liquid-containing capsules. Pouch 21is preferably formed of a liquid-permeable material such as fabric ornetting made from natural and/or synthetic materials. Alternatively,pouch 21 may be formed of a liquid-impermeable sheet material, with thebottom tip of pouch 21 either open or sealed with a rupturable sealwhich is broken upon depressing the top of pouch 21, to provide a fluidflow path to wicking layer 23.

Methods of encapsulating aqueous liquids are described for example inU.S. Pat. Nos. 3,423,489 and 3,674,704, the disclosures of which areincorporated herein by reference. As a specific example, theliquid-containing capsules may be spherical, having a diameter of up toabout 4 mm. The capsule walls are preferably formed of meltable andnon-water soluble coatings such as fats, waxes and thermoplasticpolymers. The capsules typically have a relatively uniform wallthickness of about 0.001 mm to 0.5 mm. Additional liquid-containingcapsules and methods of making same are described in the Kirk-OthmerEncyclopedia of Chemical Technology, 3rd Ed., Vol. 15, pps 470-493; and"A New Method of Preparing Monocored Water-loaded Microcapsules UsingInterfacial Polymer Deposition Process", Uno et al., Journal ofMicroencapsulation, (1984) Vol. 1, No. 1, pps 3-8.

The rounded top portion of pouch 21 is flexible allowing the user todepress the pouch in order compress the contents of the pouch therebyfracturing the capsule walls and releasing the water into wicking-layer23. When pouch 21 is formed of a liquid-permeable material such as afabric or netting, the water released from the fractured capsules freelyflows into wicking layer 23 and/or reservoir layer 15. When pouch 21 isformed of a liquid impermeable material, such as a polyethylene sheetmaterial, the bottom tip of pouch 21 must be left open or alternativelymust be formed of a rupturable seal which is ruptured upon depressingthe top portion of pouch 21. Water from the fractured capsules isthereby free to flow through the open tip of pouch 21 into layer 23and/or 15.

Pouch 21 containing water-containing capsules may be manufactured usingknown techniques. Typically, pouch 21 is manufactured using conventionalform, fill and seal techniques wherein the pouch 21 is first formed,then filled with the water-containing capsules and then appropriatelysealed. The assembled pouch 21 is then simply inserted into device 10.

Pouch 21 extends through the electronic component layer 14, the donorelectrode layer 11 but preferably not through the impermeable backinglayer 13. The donor electrode assembly 8 optionally includes a layer 23of a liquid-wicking material. Any liquid introduced through the tip ofpouch 21 is quickly wicked by layer 23 across the entire top surface ofagent reservoir 15. The pouch 21, optionally with the wicking layer 23,enables a liquid to be introduced directly into the matrix of reservoirlayer 15 in order to hydrate the matrix, and optionally to hydrate thelayers 23, 19 and/or 17 if they are present, and to activate the donorelectrode assembly 8 immediately before use. In most cases the liquidused to hydrate the matrix of reservoir 15 will be water, but otherliquids including non-aqueous liquids, can also be used to "hydrate"(i.e., activate) the matrix of reservoir layer 15. In the typical casewhere the liquid is water, the matrix of reservoir layer 15 will be atleast partly composed of a hydrophilic material such as a hydrophilicpolymer, a cellulosic sponge or pad, or other water retaining material.Most preferably, the matrix of reservoir layer 15 will be at leastpartly composed of a hydrophilic polymer of the type describedhereinafter.

As an alternative to the wicking layer 23, the top surface of reservoirlayer 15 may be provided with a plurality of grooves (not shown) influid communication with the tip of pouch 21. The grooves distribute anyliquid introduced from pouch 21 across the upper surface of reservoirlayer 15.

Similarly, a pouch 22 containing a plurality of liquid-containingcapsules is provided in the counter electrode assembly 9. Pouch 22 isformed of the same materials and using the same techniques as describedabove in connection with pouch 21. As shown, pouch 22 extends throughthe electrode layer 12 and the electronic component layer 14. Anoptional liquid wicking layer 24 may be provided between reservoir layer16 and electrode layer 12 in counter electrode assembly 9. Wicking layer24 has a similar function to wicking layer 23 in the donor electrodeassembly 8. The pouch 22, optionally with the wicking layer 24, enablesthe encapsulated liquid to be released from the capsules by depressingthe top of pouch 22 and introduced through the open or rupturable tip ofpouch 22 directly into the matrix of reservoir layer 16 in order tohydrate the matrix, and optionally to hydrate the layers 24 and/or 18 ifthere are present, and to activate the counter electrode assembly 9. Aswith the donor electrode assembly 8, the liquid used to hydrate thematrix of reservoir layer 16 will typically be water, although otherliquids including non-aqueous liquids, can also be used. As analternative to layer 24, the top surface of reservoir layer 16 may alsobe provided with a plurality of grooves which can distribute any liquidintroduced from pouch 22 across the upper surface of reservoir layer 16.

Backing layer 13 formed of a liquid impermeable material prevents liquidfrom the exterior environment from entering the device and enablesdevice 10 to be worn on the body without danger of admitting liquids,such as ordinary tap water from bathing, containing extraneous ions orother contaminants into the reservoir layers 15 and 16.

In accordance with the present invention, at least one of electrodeassemblies 8 and 9, and preferably both electrode assemblies 8 and 9 areinitially in a substantially dry state. Thus, the various iontransporting layers making up electrode assemblies 8 and 9 are initiallyin a non-hydrated condition. As used herein, the terms "dry state" and"non-hydrated" mean that the particular layer contains an insufficientamount of liquid to permit ion transport therethrough. For example, theion transmitting layers of donor electrode assembly 8 include reservoirlayer 15 and optional layers 17, 19 and 23. In order for donor electrodeassembly 8 to be considered a "dry state" electrode, none of layers 15,17, 19 and 23 are sufficiently hydrated to allow ion transporttherethrough.

Similarly, in order for counter electrode assembly 9 to be considered a"dry state" electrode, none of reservoir layer 16 or optional layers 18and 24 contains sufficient liquid to allow ion transport therethrough.

In order to be considered "non-hydrated," reservoir layers 15 and 16should generally contain less than about 10 wt % liquid, preferably lessthan about 5 wt % liquid and most preferably less than about 1 wt %liquid.

In order to activate delivery device 10, reservoir layers 15 and 16, aswell as the optional adhesive layers 17 and 18 and membrane layer 19,must become sufficiently hydrated to enable agent to be transportedtherethrough by iontophoresis. In order to hydrate reservoir layers 15and 16, as well as the optional adhesive layers 17 and 18 and membranelayer 19, an encapsulated liquid (typically water) is released from thecapsules in pouches 21 and 22.

In most cases, the liquid introduced into device 10 from pouches 21 and22 will be composed at least in part of water. However, it is wellwithin the scope of the present invention to "hydrate" the reservoirlayers 15 and 16 using other liquids including non-aqueous liquids suchas alcohols and glycols. Accordingly, as used herein, the term "hydrate"refers to the addition of either aqueous or non-aqueous based liquidsfrom pouches 21 and 22. Furthermore, in those instances where thenon-hydrated reservoir layers 15 and/or 16 initially contain no drug orelectrolyte, the encapsulated hydrating liquid may comprise a liquidsolution or suspension of the drug or electrolyte.

FIGS. 7 and 8 illustrate two alternative iontophoretic delivery devices70 and 80, respectively. In device 70, the encapsulatedliquid-containing pouches 21 and 22 are positioned at either end of thedevice. Thus, pouch 21 is positioned adjacent reservoir layer 15,optionally with a wicking layer 23 positioned between pouch 21 andreservoir layer 15. Similarly, pouch 22 is positioned adjacent reservoirlayer 16, optionally with a wicking layer 24 positioned therebetween.Device 70 is activated by squeezing pouches 21 and 22, which causes thecapsules therein to break and release liquid. The liquid is therebyintroduced either directly into reservoir layers 15 and 16, orindirectly through the wicking layers 23 and 24, respectively.Optionally, pouches 21 and 22 can be removed from device 70 afterreleasing liquid into reservoir layers 15 and 16, respectively.

FIG. 8 discloses a similar device 80 wherein the pouches 21 and 22 arepositioned on the inner sides of reservoir layers 15 and 16,respectively. Like the device illustrated in FIG. 7, device 80 is alsoactivated by squeezing pouches 21 and 22 causing the capsules to breakand release liquid into reservoir layers 15 and 16, optionally throughwicking-layers 23 and 24, respectively. As with device 70, pouches 21and 22 may optionally be removed after releasing liquid into reservoirlayers 15 and 16.

FIG. 9 discloses a similar device 90 wherein the encapsulatedliquid-containing pouches 21 and 22 are positioned at either end of thedevice, as in FIG. 7. The bottom surfaces of pouches 21 and 22 are eachcoated with an adhesive layer 17 and 18, respectively. In thisconfiguration, the pouches 21 and 22 serve both as a means to hydratereservoir layers 15 and 16, respectively, as well as a peripheraladhesive to secure device 90 to the skin. In use, appropriate releaseliners (not shown) are removed from adhesive layers 17 and 18 and device90 is secured to the skin of the patient. Pouches 21 and 22 are thendepressed in order to fracture the liquid-containing capsules therein.The liquid released from the capsules is then introduced either directlyinto reservoir layers 15 and 16, or indirectly through the wickinglayers 23 and 24, respectively.

Turning now to FIGS. 1 and 2, there is shown another iontophoretic agentdelivery device, designated by the numeral 20. As best shown in FIG. 2,device 20 has an electronic component containing layer 14 which ispreferably covered by a backing layer 13. Only the donor electrodeassembly 8 is shown in the end view of FIG. 2. Donor electrode assembly8 includes an electrode layer 11, a reservoir layer 15, and optionalmembrane layer 19 and ion-conducting adhesive layer

Device 20 includes two layers 31 and 32 which each contain a liquidsuitable for hydrating electrode assemblies 8 and 9, respectively.Layers 31 and 32 may be composed of fibrous cloth, sponge, or ahydrophilic polymer (e.g., a hydrogel) matrix material and typicallycomprise about 5 to 70 wt. % of the matrix material and about 30 to 95wt. % of the hydrating liquid.

As shown in FIGS. 1 and 2, layers 31 and 32 are initially sealed betweensheet 13b and sheets 33 and 34, respectively, and thereby isolated fromthe remaining portions of device 20. Thus, initially device 20 isseparated into two portions. One portion of device 20 contains theliquid for hydrating the device and includes the hydrated layers 31 and32, both of which are sealed between sheet 13b and sheets 33 and 34,respectively, all of which are preferably formed of a water impermeablesheet material. The other portion of device 20 is substantiallynon-hydrated and includes the electronic component layer 14, theelectrode layers 11 and 12, the reservoir layers 15 and 16 separated byinsulator 26 and optionally ion-conducting adhesive layers 17 and 18,and membrane layer 19, all of which are laminated onto sheet 13a, alsoof a preferably water impermeable material. A weakened score line 35divides sheet 13a from sheet 13b.

When device 20 is ready to be used, the sheets 33 and 34 are removed.Sheet 13b is then torn or folded along score line 35 so that layers 31and 32 are each positioned directly on sheet 13a such that layer 31covers liquid-wicking pathways 27 and layer 32 covers liquid-wickingpathways 28. Liquid-wicking pathways 27, as best shown in FIG. 2, passthrough the optional impermeable backing layer 13a, the electroniccomponent layer 14 and the electrode layer 11. Similarly, liquid-wickingpathways 28 pass through the optional backing layer 13a, the electroniccomponent layer 14 and the electrode layer 12. Thus, liquid-wickingpathways 27 extend from the exterior surface of sheet 13a to the topsurface of reservoir layer 15 while the liquid-wicking pathways 28extend from the exterior surface of sheet 13a to the top surface ofreservoir layer 16. Once the liquid-containing layers 31 and 32 areplaced over the liquid-wicking pathways 27 and 28, respectively, waterfrom layers 31 and 32 is transported along the liquid-wicking pathwaysinto the reservoir layers 15 and 16, as well as the optional layers 17,18 and 19, if they are present.

The liquid-wicking pathways 27 and 28 can take several forms. Pathways27 and 28 may be in the form of open holes running through layers 13, 14and 11 or 12, as shown in FIG. 2. Alternatively, pathways 27 and 28 maybe in the form of holes which are filled with a liquid-wicking materialwhich is effective to quickly wick liquid from gel layers 31 and 32 intoreservoir layers 15 and 16, respectively. Alternatively, pathways 27 and28 may be formed by mixing a sufficient quantity of a hydrophilicpolymer of the type used as the reservoir 15 and 16 matrices into layers13a, 14 and 11. Generally, at least about 10 wt. % and preferably atleast about 20 wt. % (on a dry weight basis) of a layer must becomprised of a hydrophilic polymer in order to provide sufficient waterwicking pathways through the layer. Thereafter, a release liner (notshown) is removed from adhesive layers 17 and 18 and the device 20 isplaced on a body surface 100 as shown in FIG. 2. FIG. 2 is an end viewof device 20 and accordingly shows only the layered configuration of the"donor" electrode assembly. It will be understood that device 20, in itsassembled condition, likewise contains an insulator 26 and a counterelectrode assembly 9.

FIG. 3 shows an end view of an alternate iontophoretic drug deliverydevice 20a, similar to device 20 shown in FIGS. 1 and 2. In device 20a,the liquid-containing layers 31 and 32 are on the opposite side of sheet13b from that shown in FIG. 2. Before use, the sheet 13b is separatedfrom sheet 13a by tearing along score line 35. The liquid-containinglayers 31 and 32 are then removed from sheet 13b and placed overliquid-wicking pathways 27 and 28, respectively. The liquid from layers31 and 32 is then wicked along pathways 27 and 28 in order to hydratethe various nonhydrated components in device 20a.

FIGS. 4 and 5 illustrate another iontophoretic delivery devicedesignated by the numeral 50. As best shown in FIG. 5, device 50 isinitially in two parts. The upper part includes the electronic componentlayer 14 and the electrode layers 11 and 12. The lower part includes theagent reservoir layers 15 and 16, liquid-containing pouches 21 and 22,insulator 26, and optional layers such as membrane layer 19,ion-conductive adhesive layers 17 and 18 and release line 38.

As best shown in FIG. 4, the bottom portion of device 50 comprises aT-shaped release liner 25 having a weakened score line 29. Agentreservoir layers 15 and 16, or optionally adhesive layers 17 and 18 ifthey are present, are releasably attached to the release liner 25. Inaddition, liquid-containing pouches 21 and 22 and insulator 26 areattached to the lower portion of release liner 25 below the score line29. In this configuration, pouches 21 and 22 are isolated from reservoirlayers 15 and 16. In the event that liquid leaks or otherwise isinadvertantly released from the pouches, there is little danger ofprematurely hydrating the electrode layers.

The device 50 can be packaged with the upper and lower portionsseparately packaged, or together with the upper portion resting on topof the lower portion but with the water-containing pouches 21 and 22 inthe position shown in FIG. 4.

Before use, the lower portion of device 50 is reconfigured by folding ortearing release liner 25 along score line 29. The liquid-containingpouches 21 and 22 are thereby moved into position between agentreservoir layers 15 and 16. In this position, the pouches 21 and 22 arein fluid communication with reservoir layers 15 and 16, respectively.The upper portion of device 50 is then pressed downwardly, as shown bythe arrows in FIG. 5, allowing pins 36 and 37 to puncture theliquid-containing pouches 21 and 22, respectively. The liquid from pouch21 is then wicked by wicking layer 23 into the non-hydrated electrodeassembly 8 in order to hydrate reservoir layer 15, and optionallymembrane layer 19 and adhesive layer 17. Likewise, liquid from the pouch22 is wicked by wicking layer 24 into the non-hydrated electrodeassembly 9 to hydrate the reservoir layer 16 and optionally the adhesivelayer 18.

In this embodiment, reservoir layers 15 and 16 are preferably comprisedof a material which becomes tacky once hydrated, e.g., a tacky hydrogel.Alternatively, the top surface of reservoir layers 15 and 16 can also becoated with a water-conducting and ion-conducting adhesive layer.

Electrical contact between reservoir layers 15-and 16 and electrodelayers 11 and 12, respectively, is maintained due to the tacky nature oflayers 15 and 16, or alternatively by an adhesive applied on the topsurfaces of layers 15 and 16. Thereafter, release liner 38 is removedfrom adhesive layers 17 and 18 and the device 50 is placed on a bodysurface for delivery of beneficial agent therethrough.

Device 50 illustrated in FIGS. 4 and 5 has particular utility when thematrices of reservoirs 15 and 16 are composed, in whole or in part, of ahydrophilic material having a tendency to swell as it absorbs thehydrating liquid. This embodiment has particular advantage when usinghydrophilic hydrogels as the matrices of reservoir layers 15 and 16,since hydrogels have a tendency to swell during hydration. Mostpreferably, the top portion of device 50 is secured onto the bottomportion of device 50 after reservoir layers 15 and 16 have beencompletely hydrated and are no longer swelling.

When used in connection with the reservoir 15 or the donor electrodeassembly 8, the term "agent" refers to beneficial agents, such as drugs,within the class which can be delivered through body surfaces. Theexpression "drug" is intended to have a broad interpretation as anytherapeutically active substance which is delivered to a living organismto produce a desired, usually beneficial, effect. In general, thisincludes therapeutic agents in all of the major therapeutic areasincluding, but not limited to, anti-infectives such as antibiotics andantiviral agents, analgesics and analgesic combinations, anesthetics,anorexics, antiarthritics, antiasthmatic agents, anticonvulsants,antidepressants, antidiabetic agents, antidiarrheals, antihistamines,anti-inflammatory agents, antimigraine preparations, antimotion sicknesspreparations, antinauseants, antineoplastics, antiparkinsonism drugs,antipruritics, antipsychotics, antipyretics, antispasmodics, includinggastrointestinal and urinary, anticholinergics, sympathomimetrics,xanthine derivatives, cardiovascular preparations including calciumchannel blockers, beta-blockers, antiarrythmics, antihypertensives,diuretics, vasodilators, including general, coronary, peripheral andcerebral, central nervous system stimulants, cough and coldpreparations, decongestants, diagnostics, hormones, hypnotics,immunosuppressives, muscle relaxants, parasympatholytics,parasympathomimetrics, proteins, peptides, psychostimulants, sedativesand tranquilizers.

The invention is particularly useful in the controlled delivery ofpeptides, polypeptides, proteins, macromolecules and other drugs whichhave a tendency to be unstable, hydrolyzed, oxidized, denatured orotherwise degraded in the presence of the liquid, such as water,necessary to conduct iontophoresis. For example, drugs containing eitheran ester bond (i.e., steroids) or an amide bond (i.e., peptides) may behydrolyzed in water. Specific examples of drugs which can becomedegraded in the presence of water include catachols, such as apomorphineand epinephrine, salbutamol, sulfhydryls such as captopril, niphedipine,and peptides such as VIP and insulin.

Examples of other peptides and proteins which may be delivered using thedevice of the present invention include, without limitation, LHRH, LHRHanalogs such as buserelin, gonadorelin, naphrelin and leuprolide, GHRH,insulin, heparin, calcitonin, endorphin, TRH, NT-36 (chemical name:N=[[(s)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide),liprecin, pituitary hormones (e.g., HGH, HMG, HCG, desmopressin acetate,etc.), follicle luteoids, αANF, growth factor releasing factor (GFRF),βMSH, somatostatin, bradykinin, somatotropin, platelet-derived growthfactor, asparaginase, bleomycin sulfate, chymopapain, cholecystokinin,chorionic gonadotropin, corticotropin (ACTH), erythropoietin,epoprostenol (platelet aggregation inhibitor), glucagon, hyaluronidase,interferon, interleukin-2, menotropins (urofollitropin (FSH) and LH),oxytocin, streptokinase, tissue plasminogen activator, urokinase,vasopressin, ACTH analogs, ANP, ANP clearance inhibitors, angiotensin IIantagonists, antidiuretic hormone agonists, antidiuretic hormoneantagonists, bradykinin antagonists, CD4, ceredase, CSF's, enkephalins,FAB fragments, IgE peptide suppressors, IGF-1, neurotrophic factors,parathyroid hormone and agonists, parathyroid hormone antagonists,prostaglandin antagonists, pentigetide, protein C, protein S, renininhibitors, thymosin alpha-1, thrombolytics, TNF, vaccines, vasopressinantagonist analogs, alpha-1 anti-trypsin (recombinant).

When used in connection with the reservoir 16 and/or the counterelectrode assembly 9, the term "agent" refers to any suitablepharmacologically acceptable electrolyte salt. Suitable electrolytesalts include water soluble and biocompatible salts such as sodiumchloride, alkali metal salts, alkaline earth metal salts such aschlorides, sulfates, nitrates, carbonates, phosphates, and organic saltssuch as ascotbates, citrates, acetates and mixtures thereof.

Electrodes 11 and 12 are electrically conductive and may be formed of ametal, or other electrically conductive material. For example,electrodes 11 and 12 may be formed of a metal foil or metal deposited orpainted on a suitable backing. Examples of suitable metals includesilver, zinc, silver/silver chloride, aluminum, platinum, stainlesssteel, gold and titanium. Alternatively, the electrodes 11 and 12 may beformed of a polymer matrix containing a conductive filler such as ametal powder, powdered graphite, carbon fibers or other knownelectrically conductive filler material. The polymer based electrodesmay be made by mixing the conductive filler in a preferably-hydrophobicpolymer matrix. For example, zinc powder, silver powder, silver/silverchloride powder, powdered carbon, carbon fibers and mixtures thereof canbe mixed in a hydrophobic polymer (e.g., an ethylene vinyl acetatecopolymer) matrix, with the preferred amount of conductive filler beingwithin the range of about 30 to 90 vol % and the remainder being thehydrophobic polymer matrix.

Electrodes 11 and 12 are electrically connected to the power source inlayer 14 using well known means, e.g., printed flexible circuits, metalfoils, wires or by direct contact. As an alternative to a battery as thepower source, device 10 can be powered by a galvanic couple formed bythe donor electrode 11 and counter electrode 12 being composed ofdissimilar electrochemical couples and being placed in electricalcontact with one other. Typical galvanic couple materials for deliveringa cationic agent include a zinc donor electrode 11 and a silver/silverchloride counter electrode 12. A Zn-Ag/AgCl galvanic couple provides anelectrical potential of about 1 volt.

The optional wicking layers 23 and 24 may be comprised of liquid-wickingmaterials such as cotton, sponges, cellulose triacetate, rayonpolyesters, hydrophilic polymer resins, etc. and blends thereof.Optionally, the passageways 21 and 22 may be filled with the same orsimilar liquid-wicking material.

The matrix of reservoirs 15 and 16 can be any material adapted to absorband hold a sufficient quantity of liquid therein in order to permittransport of agent therethrough by iontophoresis. For example, gauzesmade of cotton or other absorbent fabrics as well as pads and sponges,both natural and synthetic, may be used. Most preferably, the matrix ofreservoirs 15 and 16 is composed, at least in part, of a hydrophilicpolymer material. Both natural and synthetic hydrophilic polymers may beused. Suitable hydrophilic polymers include polyvinylpyrrolidones,polyvinyl alcohol, polyethylene oxides such as Polyox® manufactured byUnion Carbide Corp., Carbopol® manufactured by BF Goodrich of Akron,Ohio; blends of polyoxyethylene or polyethylene glycols with polyacrylicacid such as Polyox® blended with Carbopol®, polyacrylamide, Klucel®,cross-linked dextran such as Sephadex (Pharmacia Fine Chemicals, AB,Uppsala, Sweden), Water Lock® (Grain Processing Corp., Muscatine, Iowa)which is a starch-graft-poly(sodium acrylate-coacrylamide) polymer,cellulose derivatives such as hydroxyethyl cellulose,hydroxypropylmethylcellulose, low-substituted hydroxypropylcellulose,and cross-linked Na-carboxymethylcellulose such as Ac-Di-Sol (FMC Corp.,Philadelphia, Pa.), hydrogels such as polyhydroxyethyl methacrylate(National Patent Development Corp.), natural gums, chitosan, pectin,starch, guar gum, locust bean gum, and the like, along with blendsthereof. Of these, polyvinylpyrrolidones are preferred.

Optionally, the matrix of reservoirs 15 and 16 may also contain ahydrophobic, preferably heat fusible, polymer in order to enhance thelamination of reservoirs 15 and 16 to the adjacent layers. Suitablehydrophobic polymers for use in the matrix of reservoirs 15 and 16include, without limitation, polyethylene, polypropylene, polyisoprenesand polyalkenes, rubbers, copolymers such as Kraton®, polyvinylacetate,ethylene vinyl acetate copolymers, polyamides such as nylons,polyurethanes, polyvinylchloride, acrylic or methacrylic resins such aspolymers of esters of acrylic or methacrylic acid with alcohols such asn-butanol, n-pentanol, isopentanol, 2-methyl butanol, 1-methyl butanol,1-methyl pentanol, 2-methyl pentanol, 3-methyl pentanol, 2-ethylbutanol, isooctanol, n-decanol, or n-dodecanol, alone or copolymerizedwith ethylenically unsaturated monomers such as acrylic acid,methacrylic acid, acrylamide, methacrylamide, N-alkoxymethylacrylamides, N-alkoxymethyl methacrylamides, N-tertbutylacrylamide, anditaconic acid, N-branched alkyl maleamic acids wherein the alkyl grouphas 10-24 carbon atoms, glycol diacrylates, and blends thereof. Most ofthe above listed hydrophobic polymers are heat fusible. Of these,ethylene vinyl acetate copolymers are preferred.

When the drug or electrolyte is present in the reservoir matrix beforehydration, blending of the drug or electrolyte with the hydrophilicpolymer matrix components can be accomplished mechanically, either bymilling, extrusion or hot melt mixing, for example. The resultingreservoir layers may then be prepared by solvent casting, extrusion orby melt processing, for example. In addition to the drug andelectrolyte, the reservoirs 15 and 16 may also contain otherconventional materials such as dyes, pigments, inert fillers, and otherexcipients.

Insulator 26 is preferably formed of a hydrophobic non-conductingpolymeric material which is impermeable to both the passage of ions andwater. Preferred insulating materials are nonporous ethylene vinylacetate and closed cell foamed plastics.

The combined skin-contacting areas of electrode assemblies 8 and 9 canvary from less than 1 cm² to greater than 200 cm². The average device 10however, will have electrode assemblies with a combined skin-contactingarea within the range of about 5 to 50 cm².

Having thus generally described our invention and described in detailcertain preferred embodiments thereof, it will be readily apparent thatvarious modifications to the invention may be made by workers skilled inthe art without departing from the scope of this invention and which islimited only by the following claims.

What is claimed is:
 1. A multilaminate dry state electrode assembly foran electrically powered iontophoretic agent delivery device, theelectrode assembly having a reservoir layer including a substantiallynon-hydrated, hydratable matrix for containing an agent to be delivered,the reservoir layer being adapted to be placed in agent-transmittingrelation with a body surface and an electrode layer in electricalcontact with both the reservoir layer and a power source, the electrodeassembly including:means for hydrating the substantially non-hydratedmatrix, said hydrating means including a release liner comprising twoportions, said portions being joined together by a connecting means,said substantially non-hydrated matrix being located on one of saidportions and a liquid containing container being located on said otherof said portions, the container being initially isolated from, andmovable into fluid communication with, the hydratable matrix, saidconnecting means being for placing said nonhydrated matrix and saidliquid containing container in fluid communication with each other andbeing selected from the group consisting of a foldable portion and aweakened portion adapted to be torn; and means for releasing the liquidfrom the container when the container is in fluid communication with thehydratable matrix in order to hydrate the matrix and activate theelectrode assembly.
 2. The electrode assembly of claim 1, wherein theagent is unstable or becomes degraded in the presence of the liquid. 3.The electrode assembly of claim 1, wherein the electrode assembly is adonor electrode assembly and the agent is a drug.
 4. The electrodeassembly of claim 3, wherein the liquid comprises water.
 5. Theelectrode assembly of claim 3, wherein the liquid comprises an aqueoussolution of a drug.
 6. The electrode assembly of claim 3, wherein theliquid comprises an aqueous suspension of the drug.
 7. The electrodeassembly of claim 1, wherein the electrode assembly is a counterelectrode assembly and the agent is an electrolyte.
 8. The electrodeassembly of claim 7, wherein the electrolyte is a water solubleelectrolyte salt.
 9. The electrode assembly of claim 7, wherein theliquid comprises water.
 10. The electrode assembly of claim 7, whereinthe liquid comprises an aqueous solution of the electrolyte.
 11. Theelectrode assembly of claim 10, wherein the liquid comprises an aqueoussuspension of the electrolyte.
 12. The electrode assembly of claim 1,wherein the multilaminate electrode assembly includes an ion-conductingadhesive layer adapted to secure the electrode assembly to the bodysurface.
 13. The electrode assembly of claim 1, wherein themultilaminate electrode assembly includes a semipermeable membrane layerposition between the reservoir layer and the body surface.
 14. Theelectrode assembly of claim 1, wherein the matrix comprises ahydrophilic polymer.
 15. The electrode assembly of claim 1, wherein thematrix comprises a mixture of a hydrophilic polymer and a hydrophobicpolymer.
 16. The electrode assembly of claim 1, wherein the body surfaceis intact skin.
 17. The electrode assembly of claim 1, including awicking layer in fluid communication with the agent reservoir layer. 18.The electrode assembly of claim 3, wherein the means for releasing theliquid from the container comprises a pin adapted to pierce thecontainer when the electrode layer is placed in electrical contact withthe reservoir layer.
 19. The electrode assembly of claim 1, wherein thebody surface is a mucosal membrane.
 20. An electrically powerediontophoretic agent delivery device including a multilaminate dry statedonor electrode assembly and a multilaminate dry state counter electrodeassembly, the donor electrode assembly having a drug reservoir includinga substantially non-hydrated hydratable matrix for containing a drug tobe delivered, the drug reservoir being adapted to be placed in drugtransmitting relation with a body surface and a donor electrode inelectrical contact with the drug reservoir, the counter electrodeassembly having an electrolyte matrix for containing an electrolyte tobe delivered, the electrolyte reservoir being adapted to be placed inelectrolyte-transmitting relation with a body surface and a counterelectrode in electrical contact with the electrolyte reservoir;means forhydrating the substantially non-hydrated drug reservoir matrix and thesubstantially non-hydrated electrolyte reservoir matrix, said hydratingmeans including a release liner comprising two portions, said portionsbeing joined together by a connecting means, said substantiallynon-hydrated drug reservoir matrix and said substantially non-hydratedelectrolyte reservoir matrix being located on one of said portions andat least one liquid containing container being located on said other ofsaid portions, said at least one container being initially isolatedfrom, and movable into fluid communication with, at least one of thehydratable drug reservoir matrix and the hydratable electrolytereservoir matrix; said connecting means being for placing at least oneof said non-hydrated matrices and said at least one liquid containingcontainer in fluid communication with each other being selected from thegroup consisting of a foldable portion and a weakened portion adapted tobe torn; and means for releasing the liquid from the at least one liquidcontaining container when the container is in fluid communication withat least one of said hydratable drug reservoir matrix and saidhydratable electrolyte reservoir matrix in order to hydrate at least oneof the drug reservoir matrix and the electrolyte reservoir matrix andactivate at least one of the donor and counter electrode assemblies; anda source of electrical power which is electrically connected to thedonor electrode in the donor electrode assembly and the counterelectrode in the counter electrode assembly, the electrode assembliesbeing separated by an ionimpermeable separator.
 21. The device of claim20, wherein the separator is comprises of a hydrophobic polymer.
 22. Thedevice of claim 20, wherein the power source comprises a battery.
 23. Amethod of hydrating a multilaminate dry state electrode assembly in anelectrically powered iontophoretic agent delivery device, the electrodeassembly having a reservoir layer including a substantially non-hydratedhydratable matrix for containing an agent to be delivered, the reservoirlayer being adapted to be placed in agent-transmitting relation with abody surface and an electrode layer in electrical contact with a powersource and the reservoir layer, the method comprising:providing aliquid-containing container which is initially isolated form thehydratable matrix; moving the container into fluid communication withthe hydratable matrix by folding a connecting means which connects thenon-hydrated matrix with the liquid containing container; and releasingthe liquid from the container when the container is in fluidcommunication with the hydratable matrix in order to hydrate the matrixand activate the electrode assembly.
 24. The method of claim 23, whereinthe agent is unstable or becomes degraded in the presence of the liquid.25. The method of claim 23, wherein the electrode assembly is a donorelectrode assembly and the agent is a drug.
 26. The method of claim 25,wherein the liquid comprises water.
 27. The method of claim 25, whereinthe liquid comprises an aqueous solution of the drug.
 28. The method ofclaim 25, wherein the liquid comprises an aqueous suspension of thedrug.
 29. The method of claim 23, wherein the electrode assembly is acounter electrode assembly and the agent is an electrolyte.
 30. Themethod of claim 29, wherein the liquid comprises water.
 31. The methodof claim 29, wherein the liquid is an aqueous solution of theelectrolyte.
 32. The method of claim 29, wherein the liquid comprises anaqueous suspension of the electrolyte.
 33. The method of claim 23,wherein the matrix comprises a hydrophilic polymer.
 34. The method ofclaim 23, wherein the matrix comprises a mixture of a hydrophilicpolymer and a hydrophobic polymer.
 35. The method of claim 23, whereinthe liquid is released from the pouch by piercing the pouch with a pin.36. The electrode assembly of claim 1, wherein the container comprises apouch.
 37. The method of claim 23, wherein the container comprises apouch.